Clinical Scorecard: Effects of Extramedullary Disease on the Prognosis of Relapsed-Refractory Multiple Myeloma Patients Undergoing Standard Chimeric Antigen Receptor T-Cell Therapy

At a Glance

Key Highlights

• EMD occurs in 3-14% of RRMM patients and is associated with poor prognosis and treatment resistance.
• FDA-approved CAR T-cell therapies ide-cel and cilta-cel show promising response rates but EMD predicts early progression post-therapy.
• No consensus guidelines exist for EMD treatment; this study evaluates outcomes of RRMM patients with active EMD receiving commercial CAR T.

Guideline-Based Recommendations

Diagnosis

• Define active EMD as bone-independent plasma cell tumors outside bone marrow detected within 30 days before CAR T infusion.
• Use PET/CT or MRI imaging for assessment of EMD pre- and post-CAR T infusion.
• Classify high-risk cytogenetics by presence of del(17p), t(4;14), and/or t(14;16) via FISH testing.

Management

• Administer lymphodepleting chemotherapy with cyclophosphamide plus fludarabine or bendamustine prior to CAR T infusion.
• Use bridging therapy ≥14 days before lymphodepleting chemotherapy when indicated.
• Manage CRS and ICANS per ASTCT consensus criteria and institutional guidelines.
• Follow FDA-approved indications for ide-cel and cilta-cel in RRMM after ≥4 prior therapies including proteasome inhibitor, immunomodulator, and anti-CD38 antibody.

Monitoring & Follow-up

• Perform hematologic and radiographic response assessments using IMWG criteria.
• Monitor for CRS and ICANS using ASTCT grading.
• Conduct follow-up whole body imaging between days +30 and +90 post-infusion for EMD evaluation when feasible.

Risks

• EMD presence predicts early disease progression after CAR T-cell therapy.
• Potential hematologic toxicities graded per CTCAE v5.0.
• Risk of CRS and ICANS requiring close monitoring and management.

Patient & Prescribing Data

189 RRMM patients intended for commercial CAR T; 152 received infusion (108 ide-cel, 44 cilta-cel).

Patients with active EMD before CAR T infusion have poorer prognosis with early progression despite CAR T therapy; real-world data support need for tailored approaches.

Clinical Best Practices

• Careful patient selection and baseline imaging to identify active EMD prior to CAR T therapy.
• Use standardized grading systems for CRS and ICANS to guide management.
• Incorporate multidisciplinary approaches for managing high-risk RRMM with EMD.
• Ensure follow-up imaging to assess treatment response and detect early progression.
• Adjust lymphodepleting chemotherapy dosing based on renal function and institutional protocols.

References

• FDA Approval of Idecabtagene Vicleucel
• FDA Approval of Ciltacabtagene Autoleucel
• ASTCT Consensus Grading for CRS and ICANS
• International Myeloma Working Group Response Criteria